This is a broad study of alpha-1-antitrypsin deficiency and its relationship to human disease. The study is aimed at detecting those human organs susceptible to disease in the presence of alpha-1- antitrypsin deficiency. Simple screening methods are being perfected and the antitrypsin molecular variants that can predispose to disease are being determined. The mechanism whereby the Z variant for alpha-1- antitrypsin is blocked from release at its site of synthesis in the liver is being investigated. The study is also being extended to investigate the role of variations in leukocytic protease content for producing pulmonary emphysema and possibly other human disease states.